Mechanisms of lung injury will be studied in inbred Strain 13 guinea pigs and in several inbred strains of mice, particularly the Swiss strain, following intranasal injection and pulmonary infection with Mycoplasma pneumoniae or Mycoplasma pulmonis respectively. The response of the host will be examined, especially in the early stages of the infection, following inoculation of strains demonstrating marked differences in virulence. Light microscopy and ultrastructural examination will be done to study the alveolar septa for changes in epithelial cells, basement membrane, interstitial cells and interstitial inflammatory cells. Endocytic changes will be studied in the macrophages of the interstitial infiltrate and of the alveolus. Studies will also seek to evaluate the host response following modifications to the immune system by thymectomy, treatment with cyclophosphamide or by agents stimulating or inhibiting macrophages. The role of mycoplasma lipids in the immune response will be evaluated after isolating individual lipid components and reaggregating them on an homologous or heterologous mycoplasma protein (lipid-free) as a carrier. These components will be studied for their role in cell-mediated immunity in vitro by testing for lymphocyte proliferation, inhibition of macrophage migration, and cytotoxicity. Lipids also will be combined with lung tissue and tested for their ability to stimulate autoantibodies and autoimmune tissue damage. Finally, lipids will be tested for their ability to alter the immune response by immunosuppression or by changing a humoral response to a cellular response.